# Formulation to Generate Tolerance Towards Type 1 Diabetes

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $382,018

## Abstract

ABSTRACT
Currently no cure exists for the autoimmune disease Type 1 diabetes (T1D). The Juvenile Diabetes Research
Foundation estimates ~80 individuals are newly diagnosed with the disease, daily. Due to immune-mediated
destruction of the insulin-producing β cells, current treatment of T1D is limited to daily exogenous insulin
administration. What is needed are immunotherapies that selectively suppress  cell autoimmunity for the
prevention and treatment of T1D. One approach is the administration of  cell autoantigen to suppress and
tolerize diabetogenic effector T cells. Importantly, this approach avoids effects on protective immunity seen with
other T1D immunotherapies tested in the clinic. Although promising, antigen-based immunotherapy for T1D has
shown only modest clinical results. We have been studying biodegradable, acetalated dextran microparticles
(Ac-DEX MPs) as a polymeric vehicle to deliver antigen and immunomodulatory drugs. Ac-DEX MPs have a
number of properties well suited for suppressing T cell-mediated autoimmunity and reestablishing self-tolerance.
Notably, Ac-DEX MPs can be manipulated to release cargo in vivo in a tunable manner. We have shown that
timing of cargo release has marked effects on the nature and magnitude of the immune response that is elicited.
Furthermore, using this platform, we have recently shown that delivery of Ac-DEX MPs encapsulating a tolerizing
agent (rapamycin) and a  cell-derived peptide effectively prevents diabetes in an adoptive T cell transfer model
of T1D. Accordingly, the focus of the current proposal is to develop and characterize the tolerogenic properties
of Ac-DEX MPs encapsulating immunomodulatory drugs and  cell-derived peptides as a means to selectively
suppress the diabetogenic response. We hypothesize that the rate of MP degradation plus the co-encapsulation
of immunomodulatory agent enhances the tolerogenic potency of our peptide-based vaccine. To test this
hypothesis, we have proposed two Aims: Specific Aim 1: Encapsulation of rapamycin and antigens in
tunable Ac-DEX particles and optimization of particle system. Here we will establish drug, dosing, and
degradation rate of the microparticles for optimum inhibition of the autoimmune response. Specific Aim 2:
Evaluation of Ac-DEX particle formulation and mechanism of tolerance in animal models of T1D. In this
Aim, we will evaluate the trafficking of the MPs as related to immune cell uptake, characterizing the underlying
tolerogenic responses generated by the formulation, evaluate the protective and therapeutic efficacy of the
platform, and confirm that the therapy has no effect on acquired immunity.

## Key facts

- **NIH application ID:** 10310642
- **Project number:** 1R01DK130225-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Kristy M Ainslie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,018
- **Award type:** 1
- **Project period:** 2021-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10310642

## Citation

> US National Institutes of Health, RePORTER application 10310642, Formulation to Generate Tolerance Towards Type 1 Diabetes (1R01DK130225-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10310642. Licensed CC0.

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